The objective of this proposal is to define the dynamics of apoprotein metabolism in normal man, and to determine the extent to which abnormal apoprotein metabolism may contribute to human hyperlipidemic states, or participate in the pathophysiology of Ischemic heart disease, Obesity, and Diabetes. Within this context, specific examination of the dynamics of metabolism of the apoprotein components of VLDL (Very-Low-Density lipoprotein), IDL (Intermediate-Density lipoprotein), LDL (Low-Density-lipoprotein), and HDL (High-Density lipoprotein) will be pursued, with specific examination of the Apo-B, Apo-A1, Apo-A2, and Apo-C polypeptide components in vivo in man. The modulation of lipoprotein metabolism by hormones which are recognized to influence the metabolism of lipid, carbohydrate, and protein substrates and regulate their storage or delivery for tissue needs will be investigated. Thus, it is anticipated that the involvement of insulin and glucagon, as well as growth hormone, catecholamines, and cortisol, in lipoprotein regulation may be fundamental to the understanding of hyperlipemia. By extending these studies to specific pathological states in man and animals, it is anticipated that an increased appreciation of the pathogenesis of human vascular disease seen in Diabetes, Obesity, and in Ischemic Heart Disease will be obtained.